2010
DOI: 10.1016/j.neuron.2010.09.008
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Abstract: SUMMARY Itch can be suppressed by painful stimuli, but the underlying neural basis is unknown. We generated conditional null mice in which VGLUT2-dependent synaptic glutamate release from mainly Nav1.8-expressing nociceptors was abolished. These mice showed deficits in pain behaviors including mechanical pain, heat pain, capsaicin-evoked pain, inflammatory pain and neuropathic pain. The pain deficits were accompanied by greatly enhanced itching, as suggested by i) sensitization of both histamine-dependent and … Show more

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Cited by 224 publications
(208 citation statements)
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“…Very recently, two papers reported that conditional deletion of VGLUT2 from primary afferent neurons produces spontaneous scratching, leading to severe skin lesions (39,40). We did not observe this spontaneous scratching phenotype or skin lesions despite deleting VGLUT2 from a comparable, although not identical, population of primary afferent neurons.…”
Section: Methodscontrasting
confidence: 72%
See 1 more Smart Citation
“…Very recently, two papers reported that conditional deletion of VGLUT2 from primary afferent neurons produces spontaneous scratching, leading to severe skin lesions (39,40). We did not observe this spontaneous scratching phenotype or skin lesions despite deleting VGLUT2 from a comparable, although not identical, population of primary afferent neurons.…”
Section: Methodscontrasting
confidence: 72%
“…(D) Representative heat responsiveness of lamina I neurons in control and cKO mice. Raw trace (Middle) and stimulus response histogram of an isolated unit (Top) in response to innocuous and noxious heat stimuli (40,45, and 49°C; Bottom). (E) As observed for mechanical stimulation, total number of spikes of lamina I neurons in response to graded heat stimuli were significantly reduced in cKO mice (P < 0.001; n = 9 control and 20 cKO neurons).…”
Section: Vglut2 Expressionmentioning
confidence: 99%
“…Mice carrying a homozygous Nedd4L flox allele (Nedd4L fl/fl ) (30) were crossed with mice heterozygously expressing Cre recombinase under the control of the Na v 1.8 promoter (referred to as SNS-Cre), which is predominantly active in DRG nociceptive neurons (31). Cre expression in this mouse line has been extensively characterized (32) and differs from another Na v 1.8-Cre mouse line generated by the Wood laboratory (33). NEDD4-2 expression was greatly reduced in the DRG neurons of SNSNedd4L -/-mice ( Figure 4, A-E).…”
Section: Na V Expression In Sns-nedd4l -/-Knockout Micementioning
confidence: 99%
“…It is proposed that due to impairment of the nociceptive system by VGLUT2 deletion, the itch inhibitory effect of the pain processing pathway was also ablated and this, in turn, resulted in a dramatic increase in spontaneous as well as histaminedependent and independent scratching behavior. Furthermore, in animals with VGLUT2 deleted from nociceptors, capsaicin evoked mostly itch but it caused clearly pain in their littermate controls [221,222].…”
Section: Contribution Of Neural Trpv1 To Itch Sensation Induced By Vamentioning
confidence: 97%