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dc.contributor.authorHughes, Sen
dc.contributor.authorHickey, Len
dc.contributor.authorDonaldson, LFen
dc.contributor.authorLumb, BMen
dc.contributor.authorPickering, AEen
dc.date.accessioned2020-07-29T12:39:37Z
dc.date.available2020-07-29T12:39:37Z
dc.date.issued2015-02en
dc.identifier.urihttp://hdl.handle.net/10026.1/16120
dc.description.abstract

The descending noradrenergic (NAergic) projection to the spinal cord forms part of an endogenous analgesic system. After nerve injury, a localised failure in this compensatory system has been implicated as a permissive factor in the development of neuropathic sensitisation. We investigated whether restoring descending NAergic tone with intrathecal reboxetine can oppose the development of the neuropathic pain phenotype after tibial nerve transection (TNT). Rats had a lumbar intrathecal catheter implanted at the time of nerve injury for administration of reboxetine (10 μg) in both acute and chronic dosing experiments. In acute dosing experiments, both intrathecal and systemic (30 mg/kg) reboxetine partially reversed mechanical allodynia. This antiallodynic effect of intrathecal reboxetine was blocked by prior administration of yohimbine (α2-adrenoceptor antagonist, 30 μg) but not by prazosin (α1-adrenoceptor antagonist, 30 μg) or propranolol (β-adrenoceptor antagonist, 100 μg). Chronic intrathecal reboxetine (10 μg, intrathecally, twice daily for 2 weeks) suppressed the development of cold and mechanical allodynia. Nerve-injured animals demonstrated a place preference for intrathecal reboxetine, suggesting that it also reduced spontaneous pain. In contrast, an equivalent antiallodynic dose of systemic reboxetine (30 mg/kg) was aversive in both naive and TNT rats. On cessation of chronic intrathecal reboxetine, there was a gradual development of allodynic sensitisation that was indistinguishable from control TNT animals by 7 days after the end of dosing. Our results suggest that pharmacological restoration of spinal NAergic tone with intrathecal reboxetine can suppress both allodynia and spontaneous pain in the TNT model.

en
dc.format.extent328 - 334en
dc.languageengen
dc.language.isoengen
dc.subjectAdrenergic Neuronsen
dc.subjectAdrenergic Uptake Inhibitorsen
dc.subjectAnimalsen
dc.subjectInjections, Spinalen
dc.subjectMaleen
dc.subjectMorpholinesen
dc.subjectNeural Inhibitionen
dc.subjectNeuralgiaen
dc.subjectNorepinephrineen
dc.subjectRatsen
dc.subjectRats, Wistaren
dc.subjectReboxetineen
dc.titleIntrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/25599454en
plymouth.issue2en
plymouth.volume156en
plymouth.publication-statusPublisheden
plymouth.journalPainen
dc.identifier.doi10.1097/01.j.pain.0000460313.73358.31en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Psychology
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA04 Psychology, Psychiatry and Neuroscience
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA04 Psychology, Psychiatry and Neuroscience/UoA04 Psychology, Psychiatry and Neuroscience MANUAL
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeUnited Statesen
dc.identifier.eissn1872-6623en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1097/01.j.pain.0000460313.73358.31en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.typeJournal Article/Reviewen


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