Double-Blind, Placebo-Controlled, Randomized Pilot Study of Cerebral Blood Flow Patterns Employing SPECT Imaging in Dental Postsurgical Pain Patients With and Without Pain Relief

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Background Single-photon emission computed tomography (SPECT) has been employed in the study of altered regional cerebral blood flow (CBF) in experimental and chronic pain. CBF patterns have not been evaluated in patients with acute postoperative pain. Objective The purpose of this pilot study was to employ SPECT to measure CBF distribution associated with postoperative dental pain and to compare these CBF patterns to subsequent images in the same patients who were experiencing pain relief versus continued or worsening pain who had received active or placebo analgesic interventions. The primary outcome measure was the percentage change in blood flow in various regions of interest. Methods Twenty-two healthy individuals (10 males and 12 females, age range 20–29 years) who underwent the removal of ≥1 partial or full bony impacted mandibular third molars were evaluated for pain intensity as the local anesthesia dissipated, employing a 0 to10 numeric rating scale (0 = no pain; 10 = worst imaginable). When the subjects' pain level reached ≥4/10, they were injected intravenously with 260 MBq of technetium Tc 99m bicisate (ethyl cysteinate dimer). Under double-blind conditions and 10 minutes before being placed in the SPECT scanner, the first 10 subjects were randomized to receive intravenous ketorolac 15 mg or saline while the remaining 12 subjects were randomized to receive by mouth either ibuprofen 400 mg, ibuprofen 200 mg, acetaminophen 1000 mg, or placebo. One hour after drug administration, subjects were reevaluated for pain, injected with 925 MBq of technetium Tc 99m bicisate, given rescue medication if required, and then rescanned. CBF ratios were obtained for regions of interest and by normalizing to average whole brain activity. Results Subjects generally had a moderate degree (mean [SD], 7.3% [4.0%]) of thalamic asymmetry on initial scans with pain; after treatment, subjects reporting worsening pain regardless of the intervention had higher thalamic asymmetry (8.1% vs 2.8%) than those reporting relief of pain. Subjects who reported reduced pain after the intervention had significantly different ( P < 0.05) mean CBF changes compared with those reporting worsening pain in the left prefrontal cortex, left sensorimotor area, right anterior cingulate, and right caudate. Conclusions Acute postoperative dental pain was associated with moderate thalamic asymmetry that improved following successful pain management. Sustained or worsening pain was associated with increased CBF in brain regions associated with pain pathways, whereas pain relief was associated with decreased activity in the same areas.