Large A-Fiber Activity is Required for Microglial Proliferation and p38 MAPK Activation in the Spinal Cord: Different Effects of Resiniferatoxin and Bupivacaine on Spinal Microglial Changes after Spared Nerve Injury

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Large A-Fiber Activity is Required for Microglial Proliferation and p38 MAPK Activation in the Spinal Cord: Different Effects of Resiniferatoxin and Bupivacaine on Spinal Microglial Changes after Spared Nerve Injury

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dc.contributor.author Decosterd, Isabelle
dc.contributor.author Suter, Marc
dc.contributor.author Berta, Temugin
dc.contributor.author Gao, Yong-Jing
dc.contributor.author Ji, Ru-Rong
dc.date.accessioned 2011-02-20T20:34:50Z
dc.date.issued 2009
dc.identifier.citation Suter, Marc R., Temugin Berta, Yong-Jing Gao, Isabelle Decosterd, and Ru-Rong Ji. 2009. Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: Different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury. Molecular Pain 5: 53. en_US
dc.identifier.issn 1744-8069 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4728492
dc.description.abstract Background: After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK) in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX) to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1) positive fibers (mostly C- and Aδ-fibers) and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI), and observed spinal microglial changes 2 days later. Results: SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+) were microglia (Iba1+). Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord. Conclusion: (1) Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers) is not enough to prevent nerve injury-induced spinal microglial activation. (2) Peripheral input from large myelinated fibers is important for microglial activation. (3) Microglial activation is associated with mechanical allodynia. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi:10.1186/1744-8069-5-53 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759920/pdf/ en_US
dash.license LAA
dc.title Large A-Fiber Activity is Required for Microglial Proliferation and p38 MAPK Activation in the Spinal Cord: Different Effects of Resiniferatoxin and Bupivacaine on Spinal Microglial Changes after Spared Nerve Injury en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Molecular Pain en_US
dash.depositing.author Suter, Marc
dc.date.available 2011-02-20T20:34:50Z
dash.affiliation.other HMS^Anaesthesia-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Anaesthesia-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Anaesthesia-Brigham and Women's Hospital en_US

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