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dc.contributor.authorShankarappa, Sahadev A.
dc.contributor.authorTsui, Jonathan H.
dc.contributor.authorKim, Kristine N.
dc.contributor.authorReznor, Gally
dc.contributor.authorDohlman, Jenny C.
dc.contributor.authorLanger, Robert S
dc.contributor.authorKohane, Daniel S
dc.date.accessioned2013-03-05T22:16:04Z
dc.date.available2013-03-05T22:16:04Z
dc.date.issued2012-10
dc.date.submitted2012-08
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/77568
dc.description.abstractAberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain. Pharmacological blockade of that activity has been shown to mitigate the onset of associated molecular events in the nervous system. However, results in preventing onset of pain behaviors by providing prolonged nerve blockade have been mixed. Furthermore, the experimental techniques used to date to provide that blockade were limited in clinical potential in that they would require surgical implantation. To address these issues, we have used liposomes (SDLs) containing saxitoxin (STX), a site 1 sodium channel blocker, and the glucocorticoid agonist dexamethasone to provide nerve blocks lasting ∼1 wk from a single injection. This formulation is easily injected percutaneously. Animals undergoing spared nerve injury (SNI) developed mechanical allodynia in 1 wk; nerve blockade with a single dose of SDLs (duration of block 6.9 ± 1.2 d) delayed the onset of allodynia by 2 d. Treatment with three sequential SDL injections resulting in a nerve block duration of 18.1 ± 3.4 d delayed the onset of allodynia by 1 mo. This very prolonged blockade decreased activation of astrocytes in the lumbar dorsal horn of the spinal cord due to SNI. Changes in expression of injury-related genes due to SNI in the dorsal root ganglia were not affected by SDLs. These findings suggest that formulations of this kind, which could be easy to apply clinically, can mitigate the development of neuropathic pain.en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1214634109en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleProlonged nerve blockade delays the onset of neuropathic painen_US
dc.typeArticleen_US
dc.identifier.citationShankarappa, S. A. et al. “Prolonged Nerve Blockade Delays the Onset of Neuropathic Pain.” Proceedings of the National Academy of Sciences 109.43 (2012): 17555–17560. CrossRef. Web.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorLanger, Robert
dc.contributor.mitauthorKohane, Daniel S.
dc.contributor.mitauthorShankarappa, Sahadev A.
dc.contributor.mitauthorTsui, Jonathan H.
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsShankarappa, S. A.; Tsui, J. H.; Kim, K. N.; Reznor, G.; Dohlman, J. C.; Langer, R.; Kohane, D. S.en
dc.identifier.orcidhttps://orcid.org/0000-0003-0525-9479
dc.identifier.orcidhttps://orcid.org/0000-0003-4255-0492
mit.licensePUBLISHER_POLICYen_US


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