Plasticity And Function Of β Subunits Of Sodium Channel In Melittin-induced Inflammatory Pain

VGSC(voltage-gated sodium channel) are heteromeric protein complexes consisting of one large pore-forming Nav1αsubunit and one or more auxiliaryβsubunits and are essential for the generation and propagation of the action potential throughout the excitable tissues .Which have a wide distribution in the brain, neurons, skeletal and cardiac muscles. Nav1αsubunits as the core subunits of voltage-gated sodium channel play very important role in the gating and voltage-sensitive properties. However, theβsubunits of voltage-gated sodium channel called auxiliary components are also acting in a regulatory capacity. They can modulate the expression, distribution, assembly, firing frequency and gating kinetics of VGSC. There are many evidences that Changes in expression and function ofβsubunits play a major role in the genesis of peripheral hyperexcitability which occur in neuropathic pain. Such as the SNL, SNI, CCI and other neuropathic pain models.For example,VGSC transcripts were down-regulated in injured neurons except for Nav1.3, which increased, theβ2 andβ3 also increased in injured neurons but not non-injured neurons. TTX-R current densities were reduced in injured neurons and the voltage dependence of steady-state inactivation for TTX-R was positively shifted in injured and non-injured neurons. TTX-S current densities were not affected by SNI, while the rate of recovery from inactivation was accelerated in injured neurons. Auxiliaryβsubunits regulate cell-surface expression, mRNA expression and biophysical properties of Nav1αsubunits. Theβ3 andβ2 may participate in regulating the function and expression of VGSC in neuropathic pain. The expression and function of VGSC also changed in inflammatory pain. However, the function and plasticity ofβsubunits are unknown in the inflammatory pain.The purpose of this study was to examine the expression of auxiliaryβsodium channel subunits and co-expression with Nav1αsubunits such as Nav 1.8 or Nav 1.9. In this study, we first examined that the mRNA expression ofβ1-4 subunits increased in DRG and spinal after injected Melittin or CFA(Complete Freund,s Adjuvant) which is a classic inflammatory pain model, and the Nav1.8 and Nav1.9 also up-regulated. we also find the cell surface expression ofβ2 andβ3 subunits increased in DRG by Western-blotting and immunol-histochemistry. Take the fact into consideration that theβ3 subunits regulates cell surface expression of Nav1.8 ,specific disruption of the interaction betweenβ3 and Nav1.8 subunit might be a method to relieve chronic pain.