Effect of tashinone IIA on diabetic neuropathic pain in rats

Objective To investigate the effect of tanshinoneⅡA on diabetic neuropathic pain and the mechanism.Methods Eighteen male SD rats weighing 180-220 g were randomly divided into 3 groups (n=6 each):groupⅠnormal control;groupⅡdiabetes mellitus and groupⅢdiabetes mellitus + treatment.Diabetes mellitus (DM) was induced according to Aubel B,et al.Streptozotocin (STZ) 75 mg·kg~(-1) was injected intraperitoneally (IP).Three days later DM was confirmed bv blood glucose (13.3 mmol·L~(-1)).In groupⅢ1 week after STZ IP injection tanshinoneⅡA 25 mg·kg~(-1) was given IP q.d.for 2 weeks.Mechanical allodynia was measured with von Frey filaments before and at 7,14 and 27 d after STZ injection.All rats were sacrificed at 27 d after STZ injection by transcardiac perfusion with 200 ml of 4% paraformaldehyde in 0,1 mmol·L~(-1) phosphate buffer.Lumbar segment of spinal cord was removed and fixed for 10h in 4% paraformaldehyde.Paraffin slides of the spinal cord were prepared with Nissl's staining for detection of pathologic changes.The level of calcitonin gene- related peptide (CGRP) was determined by immuno-histochemistry.Results Pain threshold to mechanical stimuli in groupⅡandⅢwas significantly decreased as compared with groupⅠ(P＜0.05);while animals in groupⅢhad a higher threshold to noxious mechanical stimuli than animals in groupⅡ(P＜0.05).Microscopic examination showed that in groupⅡdorsal horn of the spinal cord was atrophic;the number of neurons were decreased and the Nissl's bodies in spinal dorsal horn neurons were diminished or vanished;while in groupⅢthese DM-induced changes were significantly attenuated.The level of CGRP in the spinal dorsal horn was significantly lower in groupⅡthan in groupⅢ.Conclusion TanshinoneⅡA an attenuate diabetic neuropathic pain and the mechanism may partly be explained by increasing the CGRP expression in spinal dorsal horn.