Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain.
Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the spared nerve injury (SNI) model of neuropathic pain and the formalin pain model in rats using positron emission tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), S1 jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral S1 hindlimb. Finally, a second cohort of SNI rats was scanned while anesthetized during the tracer uptake period, and the S1 hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in S1 hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving rodents.
Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3G 0G1, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 2T5, Canada. Electronic address: scott.thompson4@mail.mcgill.ca.
Scott J
SJ
Thompson
Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3G 0G1, Canada; Faculty of Dentistry, McGill University, Montreal, QC H3A 2T5, Canada.
Magali
M
Millecamps
Small Animal Imaging Lab, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Antonio
A
Aliaga
Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
David A
DA
Seminowicz
Division of Intramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
Lucie A
LA
Low
Small Animal Imaging Lab, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Barry J
BJ
Bedell
Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3G 0G1, Canada; Faculty of Dentistry, McGill University, Montreal, QC H3A 2T5, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Laura S
LS
Stone
Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC H3G 0G1, Canada; Faculty of Dentistry, McGill University, Montreal, QC H3A 2T5, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Petra
P
Schweinhardt
Division of Intramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
M Catherine
MC
Bushnell
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000502:physiology*; D059350:Chronic Pain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D019788:Fluorodeoxyglucose F18; D007091:Image Processing, Computer-Assisted; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D010147:Pain Measurement; D020427:Peroneal Neuropathies / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D020429:Tibial Neuropathy / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
FDG; Formalin model; MicroPET; Neuropathic pain; Spared nerve injury