Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10

Autor: Flotte Terence R, Maier Steven F, Hammack Sayamwong E, Wieseler-Frank Julie, Spataro Leah, Chacur Marucia, Cruz Pedro E, Langer Stephen J, Sloane Evan M, Milligan Erin D, Forsayeth John R, Leinwand Leslie A, Chavez Raymond, Watkins Linda R
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Zdroj: Molecular Pain, Vol 1, Iss 1, p 9 (2005)
Druh dokumentu: article
ISSN: 1744-8069
DOI: 10.1186/1744-8069-1-9
Popis: Abstract Despite many decades of drug development, effective therapies for neuropathic pain remain elusive. The recent recognition of spinal cord glia and glial pro-inflammatory cytokines as important contributors to neuropathic pain suggests an alternative therapeutic strategy; that is, targeting glial activation or its downstream consequences. While several glial-selective drugs have been successful in controlling neuropathic pain in animal models, none are optimal for human use. Thus the aim of the present studies was to explore a novel approach for controlling neuropathic pain. Here, an adeno-associated viral (serotype II; AAV2) vector was created that encodes the anti-inflammatory cytokine, interleukin-10 (IL-10). This anti-inflammatory cytokine is known to suppress the production of pro-inflammatory cytokines. Upon intrathecal administration, this novel AAV2-IL-10 vector was successful in transiently preventing and reversing neuropathic pain. Intrathecal administration of an AAV2 vector encoding beta-galactosidase revealed that AAV2 preferentially infects meningeal cells surrounding the CSF space. Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain.
Databáze: Directory of Open Access Journals