Decrease in inflammatory hyperalgesia by herpes vector-mediated knockdown of Nav1.7 sodium channels in primary afferents.
Induction of peripheral inflammation increases the expression of the Nav1.7 sodium channel in sensory neurons, potentially increasing their excitability. Peripheral inflammation also produces hyperalgesia in humans and an increase in nociceptive responsiveness in animals. To test the relationship between these two phenomena we applied a recombinant herpes simplex-based vector to the hindpaw skin of mice, which encoded both green fluorescent protein (GFP) as well as an antisense sequence to the Nav1.7 gene. The hindpaw was subsequently injected with complete Freund's adjuvant to induce robust inflammation. Application of the vector, but not a control vector encoding only GFP, prevented an increase in Nav1.7 expression in GFP-positive neurons and prevented development of hyperalgesia in both C and Adelta thermonociceptive tests. These results provide clear evidence of the involvement of an increased expression of the Nav1.7 channel in nociceptive neurons in the development of inflammatory hyperalgesia.
Yeomans
D C
DC
Department of Anesthesia and Stanford Pain and Analgesia Research Center, Stanford University, Stanford, CA 94305-5117, USA. dcyeomans@stanford.edu
Levinson
S R
SR
Peters
M C
MC
Koszowski
A G
AG
Tzabazis
A Z
AZ
Gilly
W F
WF
Wilson
S P
SP
D000818:Animals; D016373:DNA, Antisense / Q000494:pharmacology; D004274:DNA, Recombinant; D005620:Freund's Adjuvant; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006561:Herpes Simplex / Q000517:prevention & control; D006614:Hindlimb / Q000294:innervation / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D051379:Mice; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D018139:Simplexvirus / Q000235:genetics*; D015222:Sodium Channels / Q000502:physiology*
D016373:DNA, Antisense; D004274:DNA, Recombinant; D015222:Sodium Channels; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005620:Freund's Adjuvant