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The Study On Plasticity And Function Of β Subunits Of Sodium Channels In Neuropathic Pain

Posted on:2007-07-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y W WangFull Text:PDF
GTID:1104360182491774Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Objective: To investigate the plastic changes of a and β subunits of voltage-gated sodium channels in dorsal root ganglion neurons in rats resulting from a partial sciatic nerve ligation (PSNL) model of neuropathic pain, and to study the modulatory effect of β subunits on a subunits. Methods: Dorsal root ganglions(DRG) from L4L6 were removed and sectioned from PSNL rats. In situ hybridization was performed using digoxin-labelled cRNA probes of Nav 1.3, Nav1.8, β1, β2, β3. to examine the expression of subunits in PSNL model. Ooxytes were taken out and maintained in ND96 solution . The cRNA of Nav1.8, Nav1.3, or in combination of β1 or β3 was injected into Xenopus oocytes by microinjection. Whole-cell inward sodium currents were recorded using the two microelectrode voltage clamp method. Result: In situ hybridiztaion studies demonstrated that the expression of Nav1.3 subunit was significantly upregulated, the expression of Nav1.8 subunit was significantly downregulated. there were no significant changes of β1 or β2 mRNA in DRG neurons, However, β3 subunit was significantly upregulated and expressed. β1 subunit was able to enlarge peak currents of Nav1.8 channel, shift the voltage-conductance curve of Nav1.8 channel to negative, and accelerate the inactivation. β1 subunit was also able to enlarge peak currents of Nav1.3 channel, but had no effect on voltage-conductance curve of channel. β3 subunit had no effect on peak currents of Nav1.3 channel, but shifted the voltage-conductance curve to more negative, and accelerated inactivation of Nav1.3 channel. Conclusion: It is indicated that the plastic changes of Nav1.3, Nav1.8 and β3 subunits may contribute to the development of neuropathic pain. It is unlike to modulate different a subunits by one β subunit, and one a subunits by different β subunits for sodium channel.
Keywords/Search Tags:neuropathic pain, dorsal root ganglion, sodium channels, subunits
PDF Full Text Request
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