Anesth Analg 2007; 105:1784-1786
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000270206.30333.cb
ANALGESIA
The Use of Brain Positron Emission Tomography to Identify Sites of Postoperative Pain Processing With and Without Epidural Analgesia
Asokumar Buvanendran, MD*,
Amjad Ali, MD ,
Travis R. Stoub, PhD ,
Richard A. Berger, MD , and
Jeffrey S. Kroin, PhD*
From the Departments of *Anesthesiology, Radiology, Neurology, and Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois.
Address correspondence and reprint requests to Asokumar Buvanendran, MD, Department of Anesthesiology, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612. Address e-mail to Asokumar{at}aol.com.
Abstract
It is not known how different analgesic regimes affect the brain when reducing postoperative pain. We performed positron emission tomography (PET) scans on a 69-yr-old woman in the presence of moderate postoperative pain and then with epidural analgesia producing complete analgesia, during the first 2 days after total knee arthroplasty. Day 2 postsurgery PET scan data (no pain with epidural analgesia) were subtracted from Day 1 postsurgery PET scan data (time of moderate pain without epidural analgesia) to determine the brain regions activated. Postsurgical pain was 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. This study demonstrates the feasibility of evaluating the central processing of acute postoperative pain using PET.
Earlier studies have used positron emission tomography (PET) to examine the pattern of increased brain activity (measured by increased blood flow) that follows experimentally induced acute pain in volunteers (1,2) and in patients with selected chronic pain syndromes (3–5). However, no clinical study has investigated the feasibility of PET to assess changes in brain activity associated with postoperative pain. The pathophysiology of postoperative pain is not the same as that associated with chronic pain states, and is dissimilar to acute pain states induced in volunteers. Since different regions of the brain represent different pain pathways, a mapping of postoperative pain regions will allow a better understanding of how different analgesic techniques can more specifically and effectively block these pain pathways. We compared PET-imaged brain activity in a patient after total knee arthroplasty (TKA) when postoperative pain was moderate, to a subsequent postoperative PET scan taken when pain was absent due to epidural analgesia, thereby identifying regions that are activated with postoperative pain.
METHODS
After IRB approval from Rush University Medical Center and written informed consent, a 69-yr-old, right-handed, female patient scheduled for primary TKA was studied. The patient did not have any recent injuries or surgeries, and there was no history of any chronic pain syndromes beyond the pain in the joint (3-yr duration). Ten days before surgery, a brain magnetic resonance image (MRI) with a 1.5-T GE scanner (T1-SPGR, 1.6-mm gapless, 124 slices, 24-cm FOV, axial, and coronal) was obtained. Since a T1-MRI is normally stable over 2 wk, we chose to obtain the MRI presurgery to reduce the inconvenience to the patient of having to go to two different scanner locations (PET and MRI) on postoperative Day 1 or 2. The MRI was essential for colocalization of PET scan images to determine the anatomical locations. Eight days before surgery, the patient had a baseline PET scan. In a quiet room with low light and noise level, the patient was injected IV with the radionuclide 18F-fluoro-2-deoxyglucose at a dose of 4.5 mCi. After waiting 30 min, the patient’s head was positioned in the PET scanner with laser guidance, and a 3-D PET scan (10-min transmission plus 30-min emission) was performed with a Siemens ECAT EXACT 47 scanner with BGO crystal (3.1-mm-thick slices) using a PET protocol similar to that of Nofzinger et al. (6). Before the PET scan, the patient fasted for 8 h.
The patient was not taking any preoperative medication and had discontinued nonsteroidal anti-inflammatory drugs before surgery. She received a spinal anesthetic for the standard TKA procedure with epidural infusion of only local anesthetic for postoperative analgesia. No supplemental opioid was required for postoperative pain control.
Immediately after TKA surgery, pain was controlled by continuous and patient-controlled epidural infusion of 1 mg/mL bupivacaine (6–8 mL/h).The next morning, the epidural infusion was temporarily stopped with the patient’s consent. Two hours later, a PET scan was performed using the exact same protocol as for the baseline scan. After this Day 1 PET scan, the epidural infusion was immediately resumed to produce a prompt analgesic effect followed by the previous continuous and patient-controlled epidural infusion of bupivacaine. The patient had the standard physical therapy later in that day. On the second day after TKA surgery, another PET scan was performed with this maintained epidural infusion using the exact same protocol as the previous scans.
Before each PET scan, pain scores were measured using the verbal rating scale: 0 corresponding to "no pain;" 10 to the "worst imaginable pain." Digital files of PET scans were coregistered with the presurgery MRI using Analyze software (Mayo Clinic Foundation, Rochester, MN). Whole brain pixel intensities were then contrasted between scans: Day 1 postsurgery (maximum postoperative pain) minus Day 2 postsurgery (maximum analgesic effect). A relevant increase in glucose metabolism was assumed if more than 50 adjacent voxels showed a Z score >2 (5). Anatomic locations of statistically significant regions were identified according to the Montreal Neurological Institute template using SPM2 software (Wellcome Department of Cognitive Neurology, London, UK; implemented in Matlab (Mathworks, Sherborn, MA) and then converted to Talairach coordinates using MNITOTAL software (www.mrc-cbu.cam.ac.uk/Imaging/Common/mnispace.shtml). Talairach coordinates were transformed to brain areas using the Talairach Daemon program (7).
RESULTS
The pain score before TKA surgery was 2/10. On Day 1 postsurgery (with epidural analgesia stopped), the pain score just before the PET scan was 6/10. On Day 2 postsurgery (with maintained epidural analgesia), the pain score before the PET scan was 0/10. After subtracting the PET scan data of Day 2 postsurgery from that of Day 1 postsurgery, the resultant image showed increased activity in the leg area of the contralateral primary somatosensory cortex (SI) (Fig. 1A). Increased activity was not seen in the anterior cingulate cortex, insular cortex, or secondary somatosensory cortex. Other brain regions showing increased postsurgical activity (Day 1 minus Day 2) were the contralateral parietal cortex (precuneous) (Fig. 1B), bilateral pulvinar and ipsilateral medial dorsal nucleus of the thalamus (Fig. 1C), contralateral putamen (Fig. 1D), contralateral superior temporal gyrus (Fig. 1E), ipsilateral fusiform gyrus, ipsilateral posterior cerebellar lobe (uvula), and contralateral anterior cerebellar lobe (all in Fig. 1F). All regions shown in the figures were based on >100 adjacent voxels. A comparison of the presurgery baseline PET scan with the Day 2 PET scan (epidural analgesia) showed little difference in brain activation.
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Figure 1. Pain-related brain activation after left knee surgery. Six axial brain slices from superior to inferior are shown. Positron emission tomography activations are coregistered with the patient’s magnetic resonance image. Regions with Z scores >2.0 are shown in yellow-orange, and the left side of the image is the patient’s right side. Activations were detected in: A, primary somatosensory cortex (contralateral); B, right parietal cortex, precuneus (contralateral); C, thalamus (pulvinar bilateral; medial dorsal nucleus ipsilateral); D, putamen (contralateral); E, superior temporal gyrus (contralateral); F, cerebellum (bilateral), and fusiform gyrus (ipsilateral).
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DISCUSSION
PET imaging showed that postoperative pain under the conditions present in our study leads to the activation of the contralateral primary SI somatosensory cortex of the leg area. However, other areas (secondary somatosensory cortex, anterior cingulate cortex, insular cortex) that are considered integral parts of the acute pain pathway in volunteer subjects (1,2,8) did not show increased activation with postoperative pain. Our postoperative pain patient had activation of the contralateral parietal cortex (precuneous, BA7), which is different from experimentally induced acute pain (capsaicin injected into arm) which produced activity of the ipsilateral precuneous region (1). We measured activation in the contralateral superior temporal gyrus, BA22, a region not activated in acute experimentally induced pain studies (1,2). Increased activity in contralateral BA22 has been seen in patients with the chronic pain condition fibromyalgia (9). The ipsilateral fusiform gyrus, BA20, was also activated by postoperative pain, and while this region was not activated with experimentally induced acute pain (1,2), the fusiform gyrus can be excited by emotional stimulation (10), although our patient was calm throughout the trial. We also found, after knee surgery, an activation of multiple areas of the thalamus, including the medial dorsal nucleus and pulvinar, which is similar to results with the acute pain stimulus capsaicin injected into the arm (1). Motor areas were also activated during postoperative pain, and this has also been seen in experimental acute pain studies (1,2,11).
Although patient-to-patient variation is not accounted for with a single subject study, such observations can still yield important preliminary information (4,12). One factor that limits the interpretation of the findings in our patient is that the postoperative pain response may be inherently different on Day 2 compared with that on Day 1, and only a comparison that was temporally close might address this potential influence. For a full study, we could scan and compare two groups of patients on Day 1: with one group being withdrawn from epidural analgesia for a few hours, and the other group continuing to receive epidural anesthesia. In addition, factors such as attention, anticipation, and anxiety, which can influence brain activity, need to be carefully controlled for (8). Although we cannot be certain that the continuous and patient-controlled epidural infusion of 1 mg/mL bupivacaine (6–8 mL/h) on Day 2 did not have global cerebral effects in addition to the analgesic effects, the fact that only selective regions of the brain showed a difference in activation between Day 1 and Day 2 argues against this. We are aware that study of a single patient precludes definitive conclusions, but this is the first report demonstrating the feasibility of evaluating the central processing of acute postoperative pain using PET. Future prospective, randomized, controlled trials need to be performed to verify these anatomical locations for postoperative pain.
ACKNOWLEDGMENTS
The authors thank Ruth G. Ramsey, MD (MRI), Greg Lamonica (PET), Marvin A. Rossi, MD (analysis), Nithya Venkatesan (patient care), and Kenneth J. Tuman, MD (interpretation of data).
Footnotes
Accepted for publication May 1, 2007.
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