Role of Nav1.7 in dorsal root ganglia in a rat model of diabetic neuropathic pain

Objective To investigate the role of Nav1.7 in dorsal root ganglia (DRG) in a rat model of diabetic neuropathic pain (DNP).Methods Thirty-two female Wistar rats aged 3 months weighing 180-220 g were randomly divided into 4 groups ( n ＝ 8 each):control group ( group C),sham operation group ( group S),DNP group and ProTx- Ⅱ (a selective Nav1.7 blocker) group (group E).Diabetes mellitus was induced by intraperitoneal streptozocin 65 mg/kg.Blood glucose level and mechanical paw withdrawal threshold (MWT)to von Froy filamentstimulation were measured 2 weeks later.DNP was confirmed by blood glucose level ≥ 16.0 mmol/L and MWT decreased by more than 50％ of the baseline value.Intrathecal catheter was implanted at L5,6 interspace on day 10 after successful induction of DNP.On day 4 after placement of the intrathecal catheter,ProTx- Ⅱ 10 μg/kg was injected intrathecally in group E,while the equal volume of normal saline was given in groups DNP and S.MWT and never conduction velocity (NCV) were measured 1 h after intrathecal injection.The rats were then sacrificed and DRGs of the lumbar segment (L4-6) were removed for determination of Nav1.7 protein expression (by immuno-histochemistry and Western blot) and Nav1.7 mRNA expression (by RT-PCR).Results The MWT and NCV were significantly lower and the Nav1.7 mRNA and protein expression was significantly higher in groups DNP and E than in group C.ProTx- Ⅱ significantly attenuated the diabetes-induced changes in MWT,but had no effect on NCV and Nav1.7 mRNA and protein expression.Conclusion Nav1.7 in DRG is involved in the maintenance of DNP in rats. Key words: Sodium channels; Diabetes mellitus; Neuralgia; Ganglia,spinal