Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10.
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.
Milligan
Erin D
ED
Department of Psychology & the Center for Neuroscience, University of CO at Boulder, Boulder, CO 80309 USA. emilligan@psych.Colorado.edu
Sloane
Evan M
EM
Langer
Stephen J
SJ
Cruz
Pedro E
PE
Chacur
Marucia
M
Spataro
Leah
L
Wieseler-Frank
Julie
J
Hammack
Sayamwong E
SE
Maier
Steven F
SF
Flotte
Terence R
TR
Forsayeth
John R
JR
Leinwand
Leslie A
LA
Chavez
Raymond
R
Watkins
Linda R
LR
D000818:Animals; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D018836:Inflammation Mediators / Q000502:physiology*; D007278:Injections, Spinal; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000503:physiopathology*; D012585:Sciatica / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*
D018836:Inflammation Mediators; D016753:Interleukin-10