Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice.
Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit Nav1.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global Nav1.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the Nav1.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional Nav1.3 mutant mouse lines. We used Nav1.8-Cre mice to delete Nav1.3 in nociceptors at E14 and NFH-Cre mice to delete Nav1.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Nav1.3 in global knock-out mice. Our data demonstrate that Nav1.3 is neither necessary nor sufficient for the development of nerve-injury related pain.
Nassar
Mohammed A
MA
Molecular Nociception Group, Department of Biology, University College London WC1E 6BT, UK. m.nassar@ucl.ac.uk
Baker
Mark D
MD
Levato
Alessandra
A
Ingram
Rachel
R
Mallucci
Giovanna
G
McMahon
Stephen B
SB
Wood
John N
JN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D062552:NAV1.3 Voltage-Gated Sodium Channel; D009475:Neurons, Afferent / Q000473:pathology* / Q000502:physiology; D010146:Pain / Q000473:pathology* / Q000503:physiopathology*; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
D062552:NAV1.3 Voltage-Gated Sodium Channel; C515216:Scn3a protein, mouse; D015222:Sodium Channels