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.