Abstract
Ambroxol preferentially inhibits tetrodotoxin (TTX)-resistant (TTX-R), rather than TTX-sensitive (TTX-S), sodium channel α-subunit. Changes in sodium channel activity in sensory nerves have been suggested to be involved in the aberrant sensory perception in diabetes mellitus. The present study examined the effect of ambroxol on thermal hyperalgesia in diabetic mice. Treatment with ambroxol (3-30 mg/kg, p.o.) dose-dependently increased the tail-flick latency in diabetic, but not non-diabetic mice. This prolongation in diabetic mice was attenuated by pretreatment with fenvalerate (0.01 µg, i.t.). Immunoblot experiments demonstrated significant increases in the expression of TTX-S Nav1.7 and TTX-R Nav1.9 and decreases in the expression of TTX-S Nav1.6 and TTX-R Nav1.8 in the dorsal root ganglion (DRG) of diabetic mice. The expression of mRNA levels of Nav1.6, Nav1.7, Nav1.8 and Nav1.9 was not changed in the DRG of diabetic mice. These results suggest that ambroxol may be of therapeutic value against hyperalgesia in diabetes mellitus. Our present results further suggest that Nav1.9 may be an attractive target for treating the symptoms of painful diabetic neuropathies.
