Silencing the alpha(2) Subunit of gamma-aminobutyric Acid Type A Receptors in Rat Dorsal Root Ganglia Reveals Its Major Role in Antinociception Posttraumatic Nerve Injury
DC Field | Value | Language |
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dc.contributor.author | Obradovic, Aleksandar L. | - |
dc.contributor.author | Scarpa, Joseph | - |
dc.contributor.author | Osuru, Hari P. | - |
dc.contributor.author | Weaver, Janelle L. | - |
dc.contributor.author | Park, Ji-Yong | - |
dc.contributor.author | Pathirathna, Sriyani | - |
dc.contributor.author | Peterkin, Alexander | - |
dc.contributor.author | Lim, Yunhee | - |
dc.contributor.author | Jagodic, Miljenko M. | - |
dc.contributor.author | Todorovic, Slobodan M. | - |
dc.contributor.author | Jevtovic-Todorovic, Vesna | - |
dc.date.accessioned | 2021-09-04T13:14:46Z | - |
dc.date.available | 2021-09-04T13:14:46Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2015-09 | - |
dc.identifier.issn | 0003-3022 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/92679 | - |
dc.description.abstract | Background: Neuropathic pain (NPP) is likely the result of repetitive high-frequency bursts of peripheral afferent activity leading to long-lasting changes in synaptic plasticity in the spinal dorsal horn. Drugs that promote -aminobutyric acid (GABA) activity in the dorsal horn provide partial relief of neuropathic symptoms. The authors examined how in vivo silencing of the GABA receptor type A (GABA(A)) (2) gene in dorsal root ganglia (DRG) controls NPP. Methods: After crush injury to the right sciatic nerve of female rats, the (2) GABA(A) antisense and mismatch oligodeoxynucleotides or NO-711 (a GABA uptake inhibitor) were applied to the L5 DRG. In vivo behavioral assessment of nociception was conducted before the injury and ensuing 10 days (n = 4 to 10). In vitro quantification of (2) GABA(A) protein and electrophysiological studies of GABA(A) currents were performed on acutely dissociated L5 DRG neurons at relevant time points (n = 6 to 14). Results: NPP postcrush injury of a sciatic nerve in adult female rats coincides with significant down-regulation of the (2) subunit expression in the ipsilateral DRG (approximately 30%). Selective down-regulation of (2) expression in DRGs significantly worsens mechanical (2.55 0.75 to 5.16 +/- 1.16) and thermal (7.97 +/- 0.96 to 5.51 +/- 0.75) hypersensitivity in crush-injured animals and causes development of significant mechanical (2.33 +/- 0.40 to 5.00 +/- 0.33) and thermal (10.80 +/- 0.29 to 7.34 +/- 0.81) hypersensitivity in sham animals (data shown as mean +/- SD). Conversely, up-regulation of endogenous GABA via blockade of its uptake in DRG alleviates NPP. Conclusion: The GABA(A) receptor in the DRG plays an important role in pathophysiology of NPP caused by sciatic nerve injury and represents promising target for novel pain therapies. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | - |
dc.subject | CHRONIC CONSTRICTION INJURY | - |
dc.subject | SPINAL-CORD | - |
dc.subject | SCIATIC-NERVE | - |
dc.subject | SENSORY NEURONS | - |
dc.subject | PATHOLOGICAL PAIN | - |
dc.subject | EVOKED ALLODYNIA | - |
dc.subject | NEUROPATHIC PAIN | - |
dc.subject | MESSENGER-RNAS | - |
dc.subject | GLIAL UPTAKE | - |
dc.subject | IN-VIVO | - |
dc.title | Silencing the alpha(2) Subunit of gamma-aminobutyric Acid Type A Receptors in Rat Dorsal Root Ganglia Reveals Its Major Role in Antinociception Posttraumatic Nerve Injury | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Ji-Yong | - |
dc.identifier.doi | 10.1097/ALN.0000000000000767 | - |
dc.identifier.wosid | 000363536900019 | - |
dc.identifier.bibliographicCitation | ANESTHESIOLOGY, v.123, no.3, pp.654 - 667 | - |
dc.relation.isPartOf | ANESTHESIOLOGY | - |
dc.citation.title | ANESTHESIOLOGY | - |
dc.citation.volume | 123 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 654 | - |
dc.citation.endPage | 667 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Anesthesiology | - |
dc.relation.journalWebOfScienceCategory | Anesthesiology | - |
dc.subject.keywordPlus | CHRONIC CONSTRICTION INJURY | - |
dc.subject.keywordPlus | SPINAL-CORD | - |
dc.subject.keywordPlus | SCIATIC-NERVE | - |
dc.subject.keywordPlus | SENSORY NEURONS | - |
dc.subject.keywordPlus | PATHOLOGICAL PAIN | - |
dc.subject.keywordPlus | EVOKED ALLODYNIA | - |
dc.subject.keywordPlus | NEUROPATHIC PAIN | - |
dc.subject.keywordPlus | MESSENGER-RNAS | - |
dc.subject.keywordPlus | GLIAL UPTAKE | - |
dc.subject.keywordPlus | IN-VIVO | - |
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