Abstract: AIM: To investigate the relationship between TRPM3 and diabetes-induced painful peripheral neuropathy.  METHODS: Treptozotocin (STZ) was intraperitoneal injected for establishment of diabetic mice model, behavioral tests of paw withdraw thresholds (PWTs) and paw withdraw latencies (PWLs) were conducted; Protein contents and tyrosine phosphorylation levels of TRPM3 were detected by immunoprecipitation and immunoblotting. RESULTS: The PWTs and PWLs in diabetic mice were significantly reduced; TRPM3 tyrosine phosphorylation in the dorsal root ganglia (DRG) of diabetic mice significantly increased compared with control, while the protein expression shows no statistical significance; Enhanced tyrosine phosphorylation of TRPM3 by BPV can evoke heat hyperalgesia in intact mice; Reduce of the tyrosine phosphorylation levels of TRPM3 through PP2 significantly alleviates diabetes-induced heat hyperalgesia, without affecting mechanical allodynia. CONCLUSION: The upregulation of tyrosine phosphorylation of TRPM3 plays a key role in heat related painful diabetic peripheral neuropathy.

Key words: TRPM3, DRG, diabetic peripheral neuropathy, tyrosine phosphorylation, hyperalgesia, allodynia