Decrease in Inflammatory Hyperalgesia by Herpes Vector-Mediated Knockdown of Na v 1.7 Sodium Channels in Primary Afferents

Induction of peripheral inflammation increases the expression of the Na_v1.7 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 Na_v1.7 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 Na_v1.7 expression in GFP-positive neurons and prevented development of hyperalgesia in both C and Aδthermonociceptive tests. These results provide clear evidence of the involvement of an increased expression of the Na_v1.7 channel in nociceptive neurons in the development of inflammatory hyperalgesia.