3.4 Koumine reduced mechanical allodynia and anxiety-like behavior in the context of DNP
Previous studies have shown that the Gelsemium alkaloid KM possesses analgesic activities (Xiong et al., 2017), and we further evaluated the efficacy of intragastric (i.g.) administration of KM on STZ-induced mechanical hyperalgesia. Rats received either STZ or buffer injection. KM (0.28, 1.4, and 7 mg/kg) or vehicle was administered for 7 consecutive days from day 22. Behavioral tests were performed on days 7, 14, 21, and 28 at 1 hour after KM administration (Fig. 4A). Mechanical hypersensitivity was consistently present in the diabetic rats at least 4 weeks after STZ injection, indicated by a reduction in mechanical nociceptive threshold compared with their basal values or those of the control rats. Consecutive treatment of the DNP rats with KM for 7 days increased the withdrawal threshold to mechanical stimuli, although the threshold did not fully recover to the level of the control rats (Fig. 4B).
Anxiety and chronic pain are often comorbid. Next, we sought to evaluate the effect of KM on the anxiety-like behavior in the open field and elevated plus maze tests resulting from DNP (Fig. 5A). In the open field test, we observed that the DNP rats showed both decreased total distance in the open field and number of entries in the central quadrant compared to the control animals. Importantly, after 7 days of KM administration, the total distance traveled in the open field was not significantly changed, but the distance traveled in the central area of the open field was significantly increased (Fig. 5B-5D). In the elevated plus maze test, we found that the DNP rats showed both decreased time and number of entries in the open arms compared to the control rats. KM treatment increased the time spent and the number of entries into the open arms (Fig. 5E-5G). Based on these results, KM effectively improved mechanical hyperalgesia and pain-related negative emotions in the DNP rats.