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Am J Nucl Med Mol Imaging 2013;3(3):282-290
Original Article
Bilateral peripheral neural activity observed in vivo following unilateral nerve
injury
Deepak Behera, Subrat Behera, Kathleen E Jacobs, Sandip Biswal
Department of Radiology, Molecular Imaging Program at Stanford, 300 Pasteur Drive S-062B, Stanford University, CA 94304,
California, USA. These authors contributed equally to this work.
Received February 25, 2013; Accepted March 12, 2013; Epub April 9, 2013; Published April 15, 2013
Abstract: Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous
system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and
cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our
purpose is to validate manga-nese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic
pain model was created by chronic constrictive injury of the left sciatic nerve of Sprague-Dawley rats. Behavioral measurements,
using von Frey’s tests, confirmed the presence of significant allodynia in the left hind limb of animals in the injured group. T1-
weighted fast spin echo images were obtained of the lumbar cord and plexus of animals with injured left sciatic nerve and uninjured
animals (control) scanned in a 7 Tesla magnet after intraperitoneal manganese chloride administration four weeks after surgery.
Lumbar nerve roots and sciatic nerves in the injured group show increased normalized manganese-enhanced MRI signal,
representing manganese enhancement, compared to the control group. In conclusion, animals with neuropathic pain in the left hind
limb show increased manganese uptake in not only the injured sciatic nerve but also in the contralateral uninjured sciatic nerve on
manganese-enhanced MRI in vivo. Although poorly understood, this finding corroborates ex vivo finding of bilateral nociceptive-
related molecular changes in the nervous system of unilateral pain models. (ajnmmi1302005).
Keywords: Manganese-enhanced magnetic resonance imaging, chronic constrictive injury, sciatic nerve injury, neuropathic pain,
animal model
Address correspondence to: Sandip Biswal, Department of Radiology, Molecular Imaging Program at Stanford, 300 Pasteur Drive S-
068B, Stanford, CA 94305, USA. Phone: 650-498-4561; Fax: 650-725-7296; E-mail: biswals@stanford.edu
Original Article
Bilateral peripheral neural activity observed in vivo following unilateral nerve
injury
Deepak Behera, Subrat Behera, Kathleen E Jacobs, Sandip Biswal
Department of Radiology, Molecular Imaging Program at Stanford, 300 Pasteur Drive S-062B, Stanford University, CA 94304,
California, USA. These authors contributed equally to this work.
Received February 25, 2013; Accepted March 12, 2013; Epub April 9, 2013; Published April 15, 2013
Abstract: Manganese-enhanced magnetic resonance imaging (MRI) is a surrogate method to measure calcium content in nervous
system since manganese physiologically follows calcium. Manganese is detectable in MRI and therefore visualizes structures and
cell populations that actively regulate calcium. Since calcium is actively recruited for the transmission of action potentials, our
purpose is to validate manga-nese-enhanced MRI for detection of changes in lumbar nerves related to nociception. A neuropathic
pain model was created by chronic constrictive injury of the left sciatic nerve of Sprague-Dawley rats. Behavioral measurements,
using von Frey’s tests, confirmed the presence of significant allodynia in the left hind limb of animals in the injured group. T1-
weighted fast spin echo images were obtained of the lumbar cord and plexus of animals with injured left sciatic nerve and uninjured
animals (control) scanned in a 7 Tesla magnet after intraperitoneal manganese chloride administration four weeks after surgery.
Lumbar nerve roots and sciatic nerves in the injured group show increased normalized manganese-enhanced MRI signal,
representing manganese enhancement, compared to the control group. In conclusion, animals with neuropathic pain in the left hind
limb show increased manganese uptake in not only the injured sciatic nerve but also in the contralateral uninjured sciatic nerve on
manganese-enhanced MRI in vivo. Although poorly understood, this finding corroborates ex vivo finding of bilateral nociceptive-
related molecular changes in the nervous system of unilateral pain models. (ajnmmi1302005).
Keywords: Manganese-enhanced magnetic resonance imaging, chronic constrictive injury, sciatic nerve injury, neuropathic pain,
animal model
Address correspondence to: Sandip Biswal, Department of Radiology, Molecular Imaging Program at Stanford, 300 Pasteur Drive S-
068B, Stanford, CA 94305, USA. Phone: 650-498-4561; Fax: 650-725-7296; E-mail: biswals@stanford.edu
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