Matches in SemOpenAlex for { <https://semopenalex.org/work/W1570621385> ?p ?o ?g. }
Showing items 1 to 57 of
57
with 100 items per page.
- W1570621385 endingPage "82" @default.
- W1570621385 startingPage "82" @default.
- W1570621385 abstract "Top of pageAbstractIn order to determine whether increasing GABA in the spinal cord by glutamic acid decarboxylase 67 (GAD67) gene transfer to the dorsal root ganglion (DRG) would attenuate below-level central neuropathic pain resulting from spinal cord injury (SCI) we engineered a replication defective HSV based vector, deleted for the essential immediate early genes ICP4 and ICP27 and additionally deficient in expression of immediate early genes ICP22 and ICP47, to express GAD 67 driven by the HCMV IE promoter at the UL41 locus (vector QHGAD67). Transduction of DRG neurons in vitro with QHGAD67 resulted in the release of GABA measured by HPLC. Subcutaneous inoculation of the vector in the foot resulted in GAD67 expression and constitutive release of GABA in microdialysate of the dorsal horn. One week after left T13 spinal hemisection in rats, animals were inoculated subcutaneously into the plantar surface of both hindpaws with 30 microliters QHGAD67 (1x109 pfu/ml) or a lacZ-expressing control vector QOZHG. Mechanical allodynia and thermal hyperalgesia in both hindpaws was assessed with a series of calibrated von Frey filaments and Hargreaves heat apparatus, respectively. Animals inoculated with QHGAD67 demonstrated antiallodynic and antihyperalgesic effects that persisted for several weeks and could be effectively reestablished by reinoculation. The vector-mediated analgesic effects were reduced by intrathecal bicuculline or phaclofen administered at doses that produced neither mechanical allodynia nor thermal hyperalgesia. Vector-mediated GABA release attenuated the increase in spinal calcitonin gene related peptide (CGRP) caused by cord hemisection. These results demonstrate that transduction of DRG with a GAD-expressing HSV vector results in the release of GABA from nerve terminals in the spinal cord to provide an analgesic effect through actions at both GABAA and GABAB receptors, and suggests that gene therapy with a GAD67 expressing HSV based vector may prove useful in the treatment of central neuropathic pain after spinal cord injury." @default.
- W1570621385 created "2016-06-24" @default.
- W1570621385 date "2004-05-01" @default.
- W1570621385 modified "2023-10-14" @default.
- W1570621385 title "Peripherally Delivered Glutamic Acid Decarboxylase (GAD) Gene Therapy for Below-Level Spinal Cord Injury Neuropathic Pain" @default.
- W1570621385 doi "https://doi.org/10.1016/j.ymthe.2004.06.154" @default.
- W1570621385 hasPublicationYear "2004" @default.
- W1570621385 type Work @default.
- W1570621385 sameAs 1570621385 @default.
- W1570621385 citedByCount "0" @default.
- W1570621385 crossrefType "journal-article" @default.
- W1570621385 hasConcept C104317684 @default.
- W1570621385 hasConcept C111599444 @default.
- W1570621385 hasConcept C118552586 @default.
- W1570621385 hasConcept C181199279 @default.
- W1570621385 hasConcept C185592680 @default.
- W1570621385 hasConcept C2777107010 @default.
- W1570621385 hasConcept C2778334475 @default.
- W1570621385 hasConcept C2780775167 @default.
- W1570621385 hasConcept C42219234 @default.
- W1570621385 hasConcept C55493867 @default.
- W1570621385 hasConcept C71924100 @default.
- W1570621385 hasConcept C9497952 @default.
- W1570621385 hasConcept C98274493 @default.
- W1570621385 hasConceptScore W1570621385C104317684 @default.
- W1570621385 hasConceptScore W1570621385C111599444 @default.
- W1570621385 hasConceptScore W1570621385C118552586 @default.
- W1570621385 hasConceptScore W1570621385C181199279 @default.
- W1570621385 hasConceptScore W1570621385C185592680 @default.
- W1570621385 hasConceptScore W1570621385C2777107010 @default.
- W1570621385 hasConceptScore W1570621385C2778334475 @default.
- W1570621385 hasConceptScore W1570621385C2780775167 @default.
- W1570621385 hasConceptScore W1570621385C42219234 @default.
- W1570621385 hasConceptScore W1570621385C55493867 @default.
- W1570621385 hasConceptScore W1570621385C71924100 @default.
- W1570621385 hasConceptScore W1570621385C9497952 @default.
- W1570621385 hasConceptScore W1570621385C98274493 @default.
- W1570621385 hasLocation W15706213851 @default.
- W1570621385 hasOpenAccess W1570621385 @default.
- W1570621385 hasPrimaryLocation W15706213851 @default.
- W1570621385 hasRelatedWork W1965062367 @default.
- W1570621385 hasRelatedWork W1979975665 @default.
- W1570621385 hasRelatedWork W1992812138 @default.
- W1570621385 hasRelatedWork W1995275029 @default.
- W1570621385 hasRelatedWork W2008175324 @default.
- W1570621385 hasRelatedWork W2020870274 @default.
- W1570621385 hasRelatedWork W2084222240 @default.
- W1570621385 hasRelatedWork W2136718777 @default.
- W1570621385 hasRelatedWork W2901770750 @default.
- W1570621385 hasRelatedWork W4309338007 @default.
- W1570621385 hasVolume "9" @default.
- W1570621385 isParatext "false" @default.
- W1570621385 isRetracted "false" @default.
- W1570621385 magId "1570621385" @default.
- W1570621385 workType "article" @default.