Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain

Scott J. Thompson; Magali Millecamps; Antonio Aliaga; David A. Seminowicz; Lucie A. Low; Barry J. Bedell; Laura S. Stone; Petra Schweinhardt; M. Catherine Bushnell

doi:10.1016/j.neuroimage.2014.01.020

Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain

Scott J. Thompson, Magali Millecamps, Antonio Aliaga, David A. Seminowicz, Lucie A. Low, Barry J. Bedell, Laura S. Stone, Petra Schweinhardt, M. Catherine Bushnell

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26 Scopus citations

Abstract

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 30. min 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 3. weeks 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.

Original language	English (US)
Pages (from-to)	344-352
Number of pages	9
Journal	NeuroImage
Volume	91
DOIs	https://doi.org/10.1016/j.neuroimage.2014.01.020
State	Published - May 1 2014
Externally published	Yes

Bibliographical note

Funding Information:
This work was partially funded by grants to Dr. Bushnell from AstraZeneca & Pfizer Canada . This research was also partially funded by the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health. Scott J Thompson is supported by The Louise and Alan Edwards Foundation's Edwards PhD. Studentship in Pain Research.

Keywords

FDG
Formalin model
MicroPET
Neuropathic pain
Spared nerve injury

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title = "Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain",

abstract = "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 30. min 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 3. weeks 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.",

keywords = "FDG, Formalin model, MicroPET, Neuropathic pain, Spared nerve injury",

author = "Thompson, {Scott J.} and Magali Millecamps and Antonio Aliaga and Seminowicz, {David A.} and Low, {Lucie A.} and Bedell, {Barry J.} and Stone, {Laura S.} and Petra Schweinhardt and Bushnell, {M. Catherine}",

note = "Funding Information: This work was partially funded by grants to Dr. Bushnell from AstraZeneca & Pfizer Canada . This research was also partially funded by the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health. Scott J Thompson is supported by The Louise and Alan Edwards Foundation's Edwards PhD. Studentship in Pain Research. ",

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Metabolic brain activity suggestive of persistent pain in a rat model of neuropathic pain

Abstract

Bibliographical note

Keywords

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