Fig. 2. ErbB2 tyrosine kinase inhibitor reduces mechanical allodynia.
Whisker pad mechanical allodynia is alleviated by an active ErbB2 tyrosine kinase inhibitor, Lapatinib, in wild type (WT) rats with chronic constriction injury of infraorbital nerve (CCI-ION). In week 4 post CCI-ION, mechanical threshold in wild type rats was tested to confirm mechanical allodynia to von Frey filaments. Lapatinib was administered by intraperitoneal injection (vehicle, 0.2, 1 and 5mg/kg) after the pre-drug threshold was determined on both whisker pads. Bilateral behavioral responses to mechanical stimuli were monitored 30min, 1h, 3h and 6h post Lapatinib administration. (A) Lapatinib dose-dependently (Dimethyl sulfoxide (DMSO), 0.2, 1 and 5mg/kg) decreased mechanical allodynia in wild type rats with CCI-ION at 3h after drug administration. **p<0.01 at 1mg/kg, ***p<0.001 at 5mg/kg vs. DMSO. (mean±S.D) (B) Mechanical thresholds were increased by Lapatinib administration on the nerve injured side at 30min, 1h and 3h, with a maximal effect found at 3h post. *p<0.05 at 1h, ***p<0.001 at 3h vs. pre-drug. There was no change in mechanical threshold on the contralateral side after intraperitoneal injection of Lapatinib. (mean±S.D)