title: Spinal autofluorescent flavoprotein imaging in a rat model of nerve injury-induced pain and the effect of spinal cord stimulation.
abstract: Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naïve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naïve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level.
authors.affiliation: Dept. of Neurology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Joost L M
authors.initials: JL
authors.lastname: Jongen
authors.affiliation: Pain Management and Research Center, UMC+, Maastricht, the Netherlands.
authors.forename: Helwin
authors.initials: H
authors.lastname: Smits
authors.affiliation: Dept. of Neuroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pederzani
authors.affiliation: Dept. of Neuroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Malik
authors.initials: M
authors.lastname: Bechakra
authors.affiliation: Dept. of Neuroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hossaini
authors.affiliation: Dept. of Neuroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Sebastiaan K
authors.initials: SK
authors.lastname: Koekkoek
authors.affiliation: Dept. of Pain Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Frank J P M
authors.initials: FJ
authors.lastname: Huygen
authors.affiliation: Dept. of Neuroscience, Erasmus MC, Rotterdam, the Netherlands; Netherlands Institute for Neuroscience, Royal Academy for Arts and Sciences, Amsterdam, the Netherlands.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
authors.affiliation: Dept. of Neuroscience, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Holstege
authors.affiliation: Pain Management and Research Center, UMC+, Maastricht, the Netherlands.
authors.forename: Elbert A J
authors.initials: EA
authors.lastname: Joosten
mesh_terms: D000818:Animals; D005420:Flavoproteins / Q000378:metabolism*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism* / Q000628:therapy*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*; D062187:Spinal Cord Stimulation
chemical_list: D005420:Flavoproteins